Survival and periapical health after root canal treatment with carrier-based root fillings: five-year retrospective assessment.

AIM: This retrospective study explored survival and periapical healing outcomes in teeth root filled with Thermafil obturators. METHODOLOGY: Root canals of 213 teeth (94 subjects, mean age 48 ± 13 years), instrumented with a step-down technique, irrigated with 5% NaOCl and 10% EDTA and filled with Thermafil and AH Plus sealer, were involved in a recall programme. Teeth were retrospectively re-examined after 5 ± 1 years in a controlled environment. Clinical and radiographic data that were collected included the following: preoperative Periapical Index (PAI) score and signs/symptoms, treatment type, root filling length and presence/absence of voids, restoration type, follow-up PAI score and signs/symptoms. Teeth were considered 'healthy' (PAI ≤ 2, no signs/symptoms) or 'diseased' (PAI ≥ 3, signs/symptoms present, retreated, extracted for endodontic reasons). Two PAI-calibrated examiners assessed outcomes blinded to preoperative status. Bivariate and multilevel analyses were performed at level of patient and tooth (α = 5%). RESULTS: Of 213 teeth treated, 187 (88%) survived and 26 were extracted, six (3%) for persistent endodontic infection (considered 'diseased'), and 20 (9%) for root fracture, periodontal disease or coronal fracture (excluded from analysis). Whilst survival was significantly associated with tooth type (P = 0.015), type of treatment (P = 0.012) and pulpal/periapical diagnosis (P = 0.035), none of these variables were substantiated as survival predictors by the multilevel analysis. A total of 164 of 193 teeth (85%) were assessed as 'healthy', with significantly higher (chi-square; P < 0.04) 'healthy' rates for teeth with PAI score ≤2 and root fillings of adequate length. Multilevel analysis identified PAI score ≤2 (P = 0.002) as the only predictor of periapical health. CONCLUSIONS: In this 5 ± 1 year retrospective assessment, survival and healing rates after root canal treatment with Thermafil root fillings were comparable to those previously reported for conventional root filling techniques.

Supplementation with n-3, n-6, n-9 fatty acids in an insulin-resistance animal model: does it improve VLDL quality?

Insulin-resistance (IR), of increased cardiovascular risk, is characterized by the production of altered VLDL with greater atherogenicity. Dietary fatty acids influence the type of circulating VLDL. But, it is not clear how dietary fatty acids impact VLDL characteristics in IR. AIM: to evaluate the effects of n-3, n-6 and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL, in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks, SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil (SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids, glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml-1) was characterized by chemical composition and size (size exclusion-HPLC). In comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01), with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit differences in lipid and IR profile, and even favored weight gain and visceral fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 ± 4.4% vs. 68.6 ± 8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5-82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. CONCLUSION: In IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6 PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the recommendations of supplementation with these fatty acids in general diet should be revised.

Co-managed care for fragility hip fractures (Rochester model).

Hip fractures in older adults are a common event with a high risk of morbidity and mortality. Patients who sustain a hip fracture often present with multiple co-morbid conditions that can benefit from co-management by orthopedic surgeons and geriatricians. This manuscript describes a co-managed model of care for patients with hip fractures. This model of care will be explained, and the benefits and results will be described. Retrospective review of the care of all native non-pathological hip fracture patients aged 60 years and older admitted between April 2005 and March 2009 to a 261-bed community teaching hospital. The outcome measures include patient characteristics, length of stay, mortality, 30-day readmission, re-operation, and costs of care. Seven hundred fifty-eight patients were identified with an average age of 84.8 (SD 8.4); 77.8% of the patients were female, 94.7% Caucasian, and 37.3% from nursing homes, and the mean Charlson score is 2.9 (SD 2.1). The length of stay was 4.3 days, 30-day readmission rate was 10.4%, 17-month re-operation rate was 1.9%, and costs of care to the system were $15,188. The 1-year mortality rate was 21.2%. This model of care resulted in improvements in all measures studied. Previous studies have shown reduction in in-hospital complications. Additional studies are needed to show if this model of care can be translated to other systems or to other surgical conditions. Wide application of this model care could substantially improve the quality of care and cost of caring for frail elders with hip fractures.

Ortho-geriatric service--a literature review comparing different models.

In the fast-growing geriatric population, we are confronted with both osteoporosis, which makes fixation of fractures more and more challenging, and several comorbidities, which are most likely to cause postoperative complications. Several models of shared care for these patients are described, and the goal of our systematic literature research was to point out the differences of the individual models. A systematic electronic database search was performed, identifying articles that evaluate in a multidisciplinary approach the elderly hip fracture patients, including at least a geriatrician and an orthopedic surgeon focused on in-hospital treatment. The different investigations were categorized into four groups defined by the type of intervention. The main outcome parameters were pooled across the studies and weighted by sample size. Out of 656 potentially relevant citations, 21 could be extracted and categorized into four groups. Regarding the main outcome parameters, the group with integrated care could show the lowest in-hospital mortality rate (1.14%), the lowest length of stay (7.39 days), and the lowest mean time to surgery (1.43 days). No clear statement could be found for the medical complication rates and the activities of daily living due to their inhomogeneity when comparing the models. The review of these investigations cannot tell us the best model, but there is a trend toward more recent models using an integrated approach. Integrated care summarizes all the positive features reported in the various investigations like integration of a Geriatrician in the trauma unit, having a multidisciplinary team, prioritizing the geriatric fracture patients, and developing guidelines for the patients' treatment. Each hospital implementing a special model for geriatric hip fracture patients should collect detailed data about the patients, process of care, and outcomes to be able to participate in audit processes and avoid peerlessness.

Changes in bone volume and bone resorption by olpadronate treatment in an experimental model of uremic bone disease.

Thirty male adult Wistar rats (300-/+10 g body weight) underwent either 5/6 nephrectomy (Nx, n=20) or sham operation (SHAM, n=10) to determine olpadronate effects in an experimental model of uremic bone disease. For a 38-day period, 10 rats received olpadronate (16microg/100g bw) once a week (Nx+OPD) and the other vehicle (Nx). SHAM received vehicle. At baseline, treatment onset (t=7 days) and end of study (t=45 days) calcium, phosphorus, creatinine, bone alkaline phosphatase (b-ALP) and deoxypyridinoline crosslinks (DPyr) were determined. At t=0 and t=45 bone mineral density (BMD) was measured by DXA. At t=45 the right tibia was removed for bone histology. There were no differences in serum calcium. Phosphorus increased in Nx and Nx+OPD compared to SHAM (p

Shear bond strength of rebonded mechanically retentive ceramic brackets.

The purpose of this study was to evaluate the bond strength of rebonded mechanically retentive ceramic brackets. Twenty new and 100 sandblasted rebonded ceramic brackets (Clarity, 3M Unitek, Monrovia, Calif) were bonded to 120 extracted human premolars with composite resin and divided into 6 equal groups according to how the bracket bases were treated: (1) new brackets, (2) rebonded/sandblasted, (3) rebonded/sandblasted/sealant, (4) rebonded/sandblasted/hydrofluoric acid (HF), (5) rebonded/sandblasted/HF/sealant on bracket base, and (6) rebonded/sandblasted/silane. Shear bond strength of each sample was tested with a testing machine. Results showed that the new brackets group had the highest mean strength (15.66 +/- 7.05 megapascals [MPa]), followed by the rebonded/sandblasted/sealant group (7.65 +/- 5.62 MPa), the rebonded/sandblasted/silane group (5.94 +/- 5.33 MPa), the rebonded/sandblasted group (2.97 +/- 2.29 MPa), the rebonded/sandblasted/HF group (1.22 +/- 1.66 MPa), and the rebonded/sandblasted/HF/sealant group (0.82 +/- 1.16 MPa). Statistical analysis showed that only the rebonded/sandblasted/sealant group was comparable with the new brackets group in bond strength (P >.05). It was concluded that in the process of rebonding mechanically retentive ceramic brackets, (1) new brackets have the highest mean bond strength when compared with rebonded brackets, (2) the bond strength of sandblasted rebonded brackets with sealant is not significantly different from new brackets, (3) silane does not increase bond strength of rebonded brackets significantly, and (4) HF treatment on sandblasted rebonded brackets significantly decreases bond strength.

Strategic planning: going beyond the basics.

Boards are discovering that many of the strategies of the '90s that took their organizations far afield from their core mission did not pan out as intended. Now they need to take a new strategic approach--combining the basics with a view toward a dynamic health care environment.

An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro.

Hepatocytes and hepatic stellate cells play important roles in retinoid storage and metabolism. Hepatocytes process postprandial retinyl esters and are responsible for secretion of retinol bound to retinol-binding protein (RBP) to maintain plasma retinol levels. Stellate cells are the body's major cellular storage sites for retinoid. We have characterized and utilized an immortalized rat stellate cell line, HSC-T6 cells, to facilitate study of the cellular aspects of hepatic retinoid processing. For comparison, we also carried out parallel studies in Hepa-1 hepatocytes. Like activated primary stellate cells, HSC-T6 express myogenic and neural crest cytoskeletal filaments. HSC-T6 cells take up and esterify retinol in a time- and concentration-dependent manner. Supplementation of HSC-T6 culture medium with free fatty acids (up to 300 micrometer) does not affect retinol uptake but does enhance retinol esterification up to 10-fold. RT-PCR analysis indicates that HSC-T6 cells express all 6 retinoid nuclear receptors (RARalpha, -beta, -gamma, and RXRalpha, -beta, -gamma) and like primary stellate cells, HSC-T6 stellate cells express cellular retinol-binding protein, type I (CRBP) but fail to express either retinol-binding protein (RBP) or transthyretin (TTR). Addition of retinol (10(-8)-10(-5) m) or all-trans-retinoic acid (10(-10)-10(-6) m) rapidly up-regulates CRBP expression. Using RAR-specific agonists and antagonists and an RXR-specific agonist, we show that members of the RAR-receptor family modulate HSC-T6 CRBP expression.Thus, HSC-T6 cells display the same retinoid-related phenotype as primary stellate cells in culture and will be a useful tool for study of hepatic retinoid storage and metabolism.

Cadet basic training: an ethnographic study of stress and coping.

Cadet basic training (CBT) at the U.S. Military Academy at West Point is an initial cadet experience designed to transition freshmen (new cadets) into the military. Challenge is an inherent component of CBT, and some challenging activities may be stressful. However, the nature and the impact of stress on health status have not been systematically investigated. An ethnographic technique, participant observation, was used to identify stressors and coping strategies among cadets aged 18 to 21 years participating in CBT. A company of 183 cadets, consisting of 123 new cadets and 60 supervising upperclass cadets from the U.S. Military Academy, was followed throughout the 6-week CBT in the summer of 1993. The investigator observed daily activities and participated in select field training experiences. Daily field observations were taped, and field notes were generated chronicling the experience. After CBT, 10 of the 60 upperclass cadets participated in a 20-minute structured interview. Field and interview notes were systematically reviewed to identify and categorize stressors and coping techniques. Stressors included anticipatory stress, time management pressures, sleep deprivation, performance evaluations, conflicts between teamwork and competitive grading, and inexperience in the leadership role. Coping techniques identified included perceiving social support, humor, and rationalization. Three new hypotheses were generated from the observations.

Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial.

BACKGROUND: Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point. OBJECTIVE: To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene. METHODS: In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-carotene or placebo therapy for 12 additional months. RESULTS: Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. Beta-carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy. CONCLUSIONS: The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.

CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells.

Hepatic stellate cells (HSCs) are a major source of extracellular matrix, which, during fibrogenesis, undergo a process of "activation" characterized by increased proliferation and collagen synthesis. Oxidative stress can stimulate HSC proliferation and collagen synthesis in vitro. Cytochrome P4502E1 (CYP2E1) is an effective producer of reactive oxygen species. To study how intracellular oxidative stress modulates alpha 2 collagen type I (COL1A2) gene induction, a rat HSC line (HSC-T6) was transfected with human CYP2E1 complementary DNA in the sense and antisense orientation and with empty vector, and stable cell lines were generated. The cells expressing CYP2E1 displayed elevated production of reactive oxygen species and showed a 4-fold increase in COL1A2 messenger RNA (mRNA) levels; expression of this mRNA among different clones appeared to correlate with the level of CYP2E1. COL1A2 expression was decreased by vitamin E treatment or transfection with manganese superoxide dismutase, and was further increased after treatment with L-buthionine sulfoximine (BSO) to lower GSH levels. Thus, CYP2E1-dependent oxidative stress plays a major role in the elevation of COL1A2 mRNA levels in this system. Nuclear run-on assay showed a 3-and-a-half-fold increase in COL1A2 transcription in the cells expressing CYP2E1; stabilization of COL1A2 mRNA was also observed. These results indicate that under oxidative stress conditions, COL1A2 mRNA expression is regulated both transcriptionally and through mRNA stabilization. The CYP2E1-expressing HSC appear to be a valuable model for the sustained generation of reactive oxygen species and may allow the elucidation of signaling pathways responsible for oxidant stress-mediated collagen gene induction.

Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy.

Hepatic fibrosis is a wound-healing response to chronic liver injury, which if persistent leads to cirrhosis and liver failure. Exciting progress has been made in understanding the mechanisms of hepatic fibrosis. Major advances include: (i) characterization of the components of extracellular matrix (ECM) in normal and fibrotic liver; (ii) identification of hepatic stellate cells as the primary source of ECM in liver fibrosis; (iii) elucidation of key cytokines, their cellular sources, modes of regulation, and signalling pathways involved in liver fibrogenesis; (iv) characterization of key matrix proteases and their inhibitors; (v) identification of apoptotic mediators in stellate cells and exploration of their roles during the resolution of liver injury. These advances have helped delineate a more comprehensive picture of liver fibrosis in which the central event is the activation of stellate cells, a transformation from quiescent vitamin A-rich cells to proliferative, fibrogenic and contractile myofibroblasts. The progress in understanding fibrogenic mechanisms brings the development of effective therapies closer to reality. In the future, targeting of stellate cells and fibrogenic mediators will be a mainstay of antifibrotic therapy. Points of therapeutic intervention may include: (i) removing the injurious stimuli; (ii) suppressing hepatic inflammation; (iii) down-regulating stellate cell activation; and (iv) promoting matrix degradation. The future prospects for effective antifibrotic treatment are more promising than ever for the millions of patients with chronic liver disease worldwide.

Human brain metabolic response to caffeine and the effects of tolerance.

OBJECTIVE: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. METHOD: Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday. RESULTS: The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group. CONCLUSIONS: These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.

Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis.

Wound repair in the liver induces altered gene expression in stellate cells (resident mesenchymal cells) in a process known as "activation." A zinc finger transcription factor cDNA, zf9, was cloned from rat stellate cells activated in vivo. Zf9 expression and biosynthesis are increased markedly in activated cells in vivo compared with cells from normal rats ("quiescent" cells). The factor is localized to the nucleus and the perinuclear zone in activated but not quiescent cells. Zf9 mRNA also is expressed widely in nonhepatic adult rat tissues and the fetal liver. The zf9 nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine-proline clusters and leucines. The human zf9 gene maps to chromosome 10P near the telomere. Zf9 binds specifically to a DNA oligonucleotide containing a GC box motif. The N-terminal domain of Zf9 (amino acids 1-201) is transactivating in the chimeric GAL4 hybrid system. In Drosophila schneider cells, full length Zf9 transactivates a reporter construct driven by the SV40 promoter/enhancer, which contains several GC boxes. A physiologic role for Zf9 is suggested by its transactivation of a collagen alpha1(I) promoter reporter. Transactivation of collagen alpha1(I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all in D. schneider cells. Our results suggest that Zf9 may be an important signal in hepatic stellate cell activation after liver injury.

Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing.

Homology PCR has been used to identify receptor tyrosine kinases (RTKs) expressed during activation of rat hepatic stellate cells, the key fibrogenic mesenchymal element in the liver. Partial cDNAs encoding several RTKs were cloned from stellate cells activated in vivo, including those of Flt-1, Flk-1, c-met, PDGFR, and Tyro10/DDR2. RNAse protection from cells activated in vivo demonstrated biphasic induction of flt-1 and flk-1 mRNAs, receptors for vascular endothelial growth factor (VEGF). Culture-activation of stellate cells was associated with increased [125I]VEGF binding and Flt-1 and Flk-1 receptor protein. Induction of VEGF binding sites correlated with an 2.5-fold increase in DNA synthesis in response to VEGF, but only if cells were activated by growth on collagen 1, whereas cells maintained in a quiescent state on a basement membrane-like substratum (EHS matrix) were nonproliferative. In both stellate and endothelial cells VEGF-induced mitogenesis was augmented by co-incubation with basic fibroblast growth factor (bFGF), a cytokine with known synergy with VEGF. These findings suggest that the cellular targets of VEGF in liver may not be confined to sinusoidal endothelial cells, and that VEGF responses reflect combined effects on both hepatic stellate cells and sinusoidal endothelium.

Response to nutritional and growth hormone treatment in progeria.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition with an unknown molecular defect. Patients with HGP progressively develop failure to thrive (FTT), alopecia, loss of subcutaneous fat, scleroderma, stiffening of various joints, and severe atherosclerosis. The median life span is 13 years, and the main cause of death is cardiovascular complications. There are few reports of endocrine and metabolic studies because of the rarity of this condition, and the response to long-term growth hormone (GH) treatment has not been described. We report the results of endocrine and metabolic studies performed to investigate the etiology of growth failure in five patients with HGP. Additionally, the response to nutritional therapy (NT) and GH treatment in three of these patients is presented. Our results suggest that elevated GH levels are characteristic of this disease and that an elevated basal metabolic rate (BMR) could be the cause of the FTT seen in HGP. Nonaggressive NT slightly improved weight gain and growth velocity (GV). Combined NT and GH treatment in three patients improved the GV, increased the levels of growth factors, and paradoxically resulted in decreased BMRs. However, the response to these therapies decreased over time and did not seem to prevent the progression of atherosclerotic disease.

Dietary consumption and plasma concentrations of vitamin E in pregnancies complicated by preeclampsia.

OBJECTIVE: Vitamin E, a potent antioxidant, has been suggested to play a role in preventing preeclampsia. Our aim was to determine whether consumption and plasma levels of vitamin E are lower in the preeclamptic than in normal women. STUDY DESIGN: A case-control study design was used. We identified 48 women with preeclampsia (late-pregnancy hypertension, proteinuria, and hyperuricemia). Ninety normal women served as the control group. Vitamin E consumption was estimated by use of a previously validated dietary recall questionnaire administered by a single trained research nurse to 42 of the preeclamptic women and all 90 of the control women. Blood was drawn from all women and stored until assayed at -70 degrees C. Plasma vitamin E concentrations were determined by use of high-pressure liquid chromatography. RESULTS: The mean dietary vitamin E consumption was similar for both the preeclamptic and control group (11.74 +/- 9.39 vs 11.34 +/- 7.51 mg/24 hr, p = 0.73). When the analysis also included estimations of vitamin E supplements, the total consumption was found to be higher in those who had preeclampsia than in controls (37.20 +/- 20.54 vs 22.3 +/- 27.24 mg/24 hr, p = 0.003). The mean plasma vitamin E concentration was significantly higher in preeclamptic than in control patients (1.41 +/- 0.39 vs 1.15 +/- 0.32 mg/dl, p < 0.001). Among the preeclamptic patients, those with severe disease associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome (n = 11) had the highest plasma vitamin E concentrations. CONCLUSIONS: We found no evidence that low vitamin E consumption is related to the development of preeclampsia. Higher plasma vitamin E concentrations in preeclamptic patients are speculated to represent a response to oxidative stress.